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1.
二妙散对巨噬细胞分化的调控作用研究   总被引:1,自引:1,他引:0  
目的 研究二妙散对脂多糖(lipopolysaccharide,LPS)诱导巨噬细胞分化的影响。方法 噻唑蓝(methyl thiazolyltetrazolium,MTT)法测定二妙散水煎液对细胞活力的影响;将LPS (100 ng·mL-1)及不同浓度(0.1,1.0,10 mg·mL-1)的二妙散水煎液共同作用RAW264.7细胞后,酶联免疫吸附法(enzyme-linked immune sorbent assay,ELISA)检测上清液中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白介素-10(interleukin 10,IL-10)的含量,实时荧光定量PCR (Real-timefluorescent quantitative PCR,qPCR)检测RAW264.7细胞中白介素-1β(Interleukin 1β,IL-1β),IL-6的mRNA水平,Westernblot检测RAW264.7细胞NOS2的蛋白表达情况。结果 二妙散水煎液在0.01~100 mg·mL-1内对RAW264.7细胞无明显毒性。与LPS诱导的模型组相比,二妙散水煎液能明显降低细胞上清液中TNF-α的含量(P<0.05)、升高IL-10的含量(P<0.05),且可显著抑制RAW264.7细胞中M1分化标记物IL-1β、IL-6的mRNA水平(P<0.05)及NOS2的蛋白表达(P<0.05)。结论 二妙散可通过抑制巨噬细胞向M1促炎方向分化,从而发挥抗炎作用。  相似文献   

2.
红花黄色素对佐剂型关节炎大鼠的抗炎作用研究   总被引:1,自引:1,他引:0  
目的 观察红花黄色素对佐剂型关节炎大鼠的抗炎作用并探讨其机制。方法 用弗氏完全佐剂建立佐剂型关节炎大鼠模型,分为正常组、模型组、红花黄色素100,50,25 mg·kg-1组,每组10只。排水法检测大鼠足趾肿胀度,Elisa法检测炎症因子IL-1β及TNF-α的水平,western blot法检测滑膜组织中IL-1β和TNF-α蛋白的表达。结果 与模型组相比,红花黄色素各组能显著降低佐剂型关节炎大鼠的足趾肿胀度(p<0.01或P<0.05),降低血清中IL-1β及TNF-α含量水平(p<0.01或p<0.05),还能降低滑膜组织中IL-1β及TNF-α蛋白的表达(p<0.01或p<0.05)。结论 红花黄色素能显著缓解佐剂型关节炎大鼠的关节炎症,其机制与下调炎症因子IL-1β及TNF-α的表达有关。  相似文献   

3.
目的 研究安络小皮伞醇提取物(MAEE)对坐骨神经慢性压迫性损伤(CCI)所致神经病理性疼痛大鼠的镇痛作用并探索其作用机制。方法 40只成年SD大鼠随机分为假手术组、模型组及MAEE高、中、低剂量(800、400、200 mg/kg)组,每组8只。CCI术后14 d,连续ig给药7 d。于1、3、5、7 d给药后2 h测定大鼠机械痛阈(MWT)值和热痛阈(TWL)值,并在停药后连续测定3 d。于给药7 d后,取各组大鼠脊髓L4-L6节段,ELISA及实时荧光定量PCR(qRT-PCR)法检测炎症因子肿瘤坏死因子-α(TNF-α)及白细胞介素-1β(IL-1β)的表达,Western blotting法检测MAPK家族蛋白p-ERK、p-p38、p-JNK的表达变化。结果 与模型组比较,连续7 d给予MAEE能够剂量依赖性的缓解CCI诱导的大鼠机械学过敏及热痛学超敏(P<0.05、0.01);下调CCI大鼠脊髓L4-L6节段炎症因子TNF-α和IL-1β的水平以及p-ERK、p-p38、p-JNK的蛋白表达(P<0.05、0.01)。结论 MAEE剂量依赖性的缓解CCI诱导的机械学超敏及热痛学过敏,该作用可能与其抑制CCI大鼠脊髓TNF-α、IL-1β等炎性细胞因子的表达及降低MAPK磷酸化蛋白表达相关。  相似文献   

4.
目的 考察灵仙新苷对大鼠心肌缺血再灌注损伤(MIRI)的保护作用,并阐述可能的作用机制。方法 SD大鼠随机分为6组:假手术组、模型组、丹参酮ⅡA(阳性药,16 mg/kg)组和灵仙新苷低、中、高(8、16、32 mg/kg)组,连续ig给药7 d;采用结扎冠状动脉左前降支法制备大鼠MIRI模型,缺血40 min再灌120 min;试剂盒法检测MIRI大鼠血清肿瘤坏死因子-α(TNF-α)、白介素-1β(IL-1β)、白介素-6(IL-6)水平;TTC染色法检测心肌梗死率,流式细胞术检测心肌细胞凋亡率;Western blotting法检测心肌组织中Bcl-2、Bax、TNF-α及Caspase-3的蛋白表达水平。结果 与模型组比较,灵仙新苷(8、16、32 mg/kg)显著降低MIRI模型大鼠血清中TNF-α、IL-1β、IL-6水平,心肌梗死率和心肌细胞凋亡率;明显上调Bcl-2蛋白表达水平,下调Bax、TNF-α、Caspase-3蛋白表达水平,且均具有显著性差异(P<0.05、0.01)。结论 灵仙新苷对MIRI大鼠心肌具有保护作用,其机制可能与抑制TNF-α,调节Bcl-2/Bax蛋白平衡,减少MIRI诱导的心肌细胞凋亡有关。  相似文献   

5.
目的 评价湖北金粟兰中倍半萜二聚体化合物(+)-chlorahupetenes B[(+)-CHB]对脂多糖(LPS)诱导的小鼠巨噬细胞(RAW264.7)炎症反应的影响及作用机制。方法 RAW264.7细胞分为对照组(给予等体积DMSO)、模型组(给予等体积DMSO)、地塞米松磷酸钠注射液(Dex,阳性对照,1 μmol·L-1)组和(+)-CHB低、中、高浓度(5、10、20 μmol·L-1)组。各组分别加入相应药物孵育细胞1 h,除对照组外,其余组加入LPS (1 μg·mL-1)诱导24 h造成炎症应答模型。细胞增殖检测法用于评估细胞活力;Griess反应检测一氧化氮(NO)浓度;酶联免疫分析检测炎症细胞因子肿瘤坏死因子α(TNF-α)、白细胞介素(IL)-1β、IL-6的生成;实时荧光定量PCR (qRT-PCR)检测IL-1β、NOD样受体热蛋白结构域相关蛋白3(NLRP3)、环氧合酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、IL-6TNF-α mRNA表达;Western blotting检测Toll样受体4(TLR4)、髓样分化因子88(MyD88)、核因子κB (NF-κB) p65、p-NF-κB p65、NLRP3、嘌呤能受体(P2X7)蛋白表达水平。结果 与模型组比较,(+)-CHB减少了梭形细胞数量,使大部分细胞恢复正常形态;显著抑制NO、TNF-α、IL-6、IL-1β生成(P<0.01),显著降低COX-2、iNOS、IL-6、TNF-α、NLRP3、IL-1β mRNA水平(P<0.05、0.01);显著降低TLR4、MyD88、NF-κB p65、p-NF-κBp65、NLRP3、P2X7蛋白表达水平(P<0.05、0.01)。结论 (+)-CHB通过抑制TLR4/MyD88/NF-κB信号通路和P2X7/NLRP3/IL-1β炎症小体轴激活缓解LPS诱导的巨噬细胞炎症反应。  相似文献   

6.
目的 验证炎调方对脓毒症急性肺损伤(ALI)大鼠的保护效应,并观察炎调方对核因子κB(NF-κB)信号通路主要指标活性调控的时效关系。方法 清洁级健康雄性SD大鼠随机分为假手术组、模型组、炎调方(生药量为9.9 g/kg)组、地塞米松(0.45 mg/kg)组,均每天ig给药1次,连续给药3 d。假手术组、模型组予等体积生理盐水,末次给药2 h后进行手术。采用盲肠结扎穿孔术(CLP)制备脓毒症ALI模型,各组分别于造模后4、6、8、10、12、18、24 h进行HE染色后肺组织损伤程度评分、检测肺组织NF-κB/p65 mRNA表达量和血清NF-κB、肿瘤坏死因子(TNF-α)、白细胞介素(IL)-1β、IL-6、IL-8水平。结果 与模型组比较,炎调方组造模后12、18、24 h肺组织损伤程度评分均显著降低(P<0.01)。炎调方组和地塞米松组肺组织NF-κB/p65 mRNA相对表达量、血清NF-κB水平均显著低于模型组(P<0.01);高于假手术组(P<0.01);炎调方组大鼠肺组织NF-κB/p65 mRNA相对表达量、血清NF-κB均随CLP后时间的延长呈现上升趋势,12 h后变化趋缓。不同时间点炎调方组和地塞米松组血清TNF-α、IL-1β、IL-6、IL-8均显著低于模型组(P<0.01),显著高于假手术组(P<0.01);炎调方组血清TNF-α、IL-1β、IL-6、IL-8随CLP后时间的延长呈现上升趋势。脓毒症ALI大鼠肺组织NF-κB/p65mRNA相对表达量与血清NF-κB和促炎因子TNF-α、IL-1β、IL-6、IL-8水平呈强正相关。结论 炎调方对脓毒症ALI大鼠肺组织保护效应的机制与下调NF-κB基因表达、进而下调炎性信号通路下游的促炎细胞因子水平相关。  相似文献   

7.
目的 比较雷公藤柱层析各段组分对Ⅱ型胶原诱导性关节炎(collagen-induced arthritis,CIA)模型大鼠血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)表达的影响,初步探讨各段组分中有效成分与药效的关系。方法 HPLC测定各段组分中6个有效成分的含量。在SD大鼠背、尾根及左后足跖多点皮内注射牛Ⅱ型胶原蛋白(BCⅡ)乳液,建立CIA大鼠模型。选取80只成模大鼠随机分为模型对照组、阳性对照组和各段组分组,每组各8只。免疫20 d后,连续灌胃给药3周,记录大鼠关节炎指数(arthrits index,AI),通过酶联免疫法检测血清中TNF-α、IL-1β的表达,原位末端转移酶标记技术(TUNEL染色法)检测各段组分对肝细胞凋亡的影响,Western-blot检测大鼠肝组织中caspase-3蛋白表达。结果 中段和末段组分中有效成分的含量差异较大。与模型对照组比较,中段组分的高、低剂量组和末段组分的高剂量组给药3周后均能明显降低AI值(P<0.01),能明显抑制大鼠血清中TNF-α、IL-1β表达(P<0.01),也能明显诱导肝细胞凋亡(P<0.01),明显升高caspase-3活性(P<0.01)。结论 雷公藤柱层析各段组分治疗CIA可能与降低血清中TNF-α和IL-1β表达有关,灌胃后会诱导大鼠肝细胞发生凋亡,上调caspase-3活性,有效成分与药效存在量效关系。  相似文献   

8.
目的 研究少腹逐瘀汤对输卵管炎性不孕大鼠Nod样受体蛋白3(NLRP3)炎症小体的作用。方法 采用金黄色葡萄球菌法构建大鼠输卵管炎性不孕模型,造模成功雌性大鼠随机分为3组:模型组、少腹逐瘀汤(以生药计5g·kg-1,临床等效剂量)组、盐酸左氧氟沙星(阳性药,80mg·kg-1)组,另取10只大鼠作为对照组。各组于成模后第8天开始ig给药,每天1次,连续30d,对照组和模型组ig等量0.9%氯化钠注射液。各组雌鼠与成熟雄鼠按2∶1合笼,观察受孕率;HE染色观察各组大鼠输卵管病理变化;Western blotting法检测输卵管组织中NLRP3蛋白表达;实时荧光定量PCR(qRTPCR)法检测输卵管组织中NLRP3和白细胞介素-1β(IL-1β)mRNA水平。原代培养大鼠输卵管上皮细胞,10nmol·L-1脂多糖(LPS)刺激24h制备炎症模型,造模同时给予10mg·L-1盐酸左氧氟沙星、10mg·L-1少腹逐瘀汤处理,Western blotting法检测细胞NLRP3蛋白表达;qRT-PCR法检测细胞中NLRP3IL-1β、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)mRNA水平。结果 对照组的受孕率为60%,模型组的受孕率为40%,盐酸左氧氟沙星组和少腹逐瘀汤组的受孕率均为80%。对照组大鼠输卵管结构清晰,黏膜皱褶丰富,黏膜上皮细胞排列整齐,管腔通畅;模型组大鼠的输卵管结构分界欠清,黏膜皱褶消失,黏膜上皮细胞排列紊乱,管腔狭窄,出现梗阻和大量炎性细胞浸润等情况;盐酸左氧氟沙星组与少腹逐瘀汤组大鼠输卵管结构有改善,管壁组织结构尚清晰,黏膜上皮细胞排列欠规整,管腔通畅,仅少量炎性细胞浸润。与对照组比较,模型组大鼠输卵管组织的NLRP3蛋白和NLRP3、IL-1βmRNA水平显著上调(P<0.001);与模型组比较,少腹逐瘀汤组输卵管组织的NLRP3蛋白和NLRP3、IL-1βmRNA水平显著下降(P<0.05、0.001)。与对照组比较,模型组输卵管上皮细胞NLRP3蛋白和NLRP3IL-1βIL-6TNF-αmRNA水平显著上调(P<0.05、0.01、0.001);与模型组比较,少腹逐瘀汤组NLRP3蛋白和NLRP3IL-1βIL-6TNF-αmRNA水平显著下降(P<0.05、0.01)。结论 少腹逐瘀汤治疗输卵管炎性不孕症的作用机制可能与调节NLRP3介导的炎症反应有关。  相似文献   

9.
依普利酮对糖尿病肾病大鼠的保护机制研究   总被引:1,自引:1,他引:0  
目的 探讨依普利酮对糖尿病肾病(diabetic nephropathy,DN)大鼠的保护机制。方法 DN模型大鼠随机分成模型组、依普利酮组(40 mg·kg-1)、阳性对照组(缬沙坦,20 mg·kg-1),另设正常组。灌胃给药8周。全自动生化分析仪检测24 h尿蛋白、血肌酐及血糖化血红蛋白水平;HE染色行肾组织病理形态学观察;ELISA检测肾组织IL-6、TNF-α和MCP-1水平;qPCR检测TLR4、NF-κB p65 mRNA水平,Western blot法检测肾组织TLR4、NF-κB p65蛋白水平。结果 与模型组比较,依普利酮组大鼠24 h尿蛋白、血肌酐及血糖化血红蛋白水平均明显下降(P<0.05或P<0.01);肾组织病理变化有不同程度的改善;肾组织IL-6、TNF-α和MCP-1水平均明显下降(P<0.05或P<0.01),TLR4、NF-κB p65 mRNA水平和TLR4、NF-κB p65蛋白水平明显下降(P<0.01)。结论 依普利酮能有效地改善DN大鼠的炎症水平,机制可能与下调IL-6、TNF-α、MCP-1、TLR4、NF-κB p65水平有关。  相似文献   

10.
目的 探讨止痛化癥胶囊联合左氧氟沙星治疗慢性盆腔炎的临床疗效。方法 选取2019年9月—2021年2月在泰州市人民医院就诊的106例慢性盆腔炎患者作为研究对象,按照治疗方法将所有患者分为对照组和观察组,各53例。对照组口服左氧氟沙星片,0.1 g/次,3次/d。观察组在对照组基础上口服止痛化癥胶囊,1.2 g/次,3次/d。连续治疗2周。观察两组的临床疗效,比较患者治疗前后的视觉模拟评分法(VAS)评分、炎性包块的最长直径,以及血清中人巨噬细胞趋化蛋白-1(MCP-1)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的水平。结果 治疗后,观察组的总有效率为94.34%,对照组为81.13%,两组比较差异有统计学意义(P<0.05)。治疗后,两组VAS评分均显著降低,盆腔炎性包块的最长直径显著减少(P<0.05);且观察组显著低于对照组(P<0.05)。治疗后,两组的MCP-1、TNF-α、IL-6水平均显著降低(P<0.05);治疗后,观察组的MCP-1、TNF-α、IL-6水平显著低于对照组,差异有统计学意义(P<0.05)。结论 止痛化癥胶囊联合左氧氟沙星片治疗慢性盆腔炎的疗效确切,能减轻疼痛程度,缩小炎性包块大小,降低炎症反应,值得临床推广运用。  相似文献   

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Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.
Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.
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This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.  相似文献   

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Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.  相似文献   

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The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.  相似文献   

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Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.  相似文献   

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In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.  相似文献   

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